The present invention relates in general to cardiovascular measurement and more particularly to methods and systems for determining cardiac contractility.
Throughout this application, various publications and patents are referred to by an identifying citation. The disclosures of the publications and patents referenced in this application are hereby incorporated by reference into the present disclosure to more fully describe the state of the art to which this invention pertains.
Almost any cardiac disorder that impairs the ability of the ventricle to eject blood suffers a progression toward an inexorable deterioration of cardiac structure and function, producing the complex clinical syndrome of heart failure, which is a common medical condition that afflicts approximately 1.5 to 2.0% of the population (4.8 million people in the United States) and which has a risk of death of 5 to 10% annually in patients with mild symptoms and increases to as high as 30 to 40% annually in patients with advanced disease, as, for example, described in 1998 Heart and Stroke Statistical Update by the American Heart Association, Dallas, Tex., 1997; Am. Heart J., Vol. 133, pages 703 to 712 (1997) by Massie et al.;J. Heart Lung Transplant, Vol. 13, pages S107 to S112 (1994) by O""Connell et al.; and Am. Coll. Cardiol., Vol. 22 (Suppl. A.), pages 6A to 13A (1993) by Ho et al. Annual direct expenditures for heart failure in the United States have been estimated at $20 to 40 billion, twice that for all forms of cancer, as described in the above-mentioned references by Massie et al. and O""Connell et al.
The core of the altered cardiac function in heart failure is a depression of cardiac contractility, as, for example, described in Lancet, Vol. 352 (Suppl. I), pages 8 to 14 (1998) by Bristow. Therefore, an adequate assessment of cardiac contractility has important diagnostic and therapeutic implications. Patients with acute heart failure, particularly as a complication of acute myocardial infarction or as an acute exacerbation of a previously compensated chronic heart failure, have a high mortality rate of about 30% within the first 12 months. In this clinical condition, a proper evaluation of cardiac contractility is extremely important for diagnostic purposes to assess the severity of the process and as a guide for the inotropic therapy. Typically, ejecting phase indices are used to evaluate ventricular function with the serious limitations that these parameters have, especially in this clinical setting where frequent and prominent hemodynamic load changes occur, as, for example, described in Arch. Mal. Coeur. Vaiss., Vol. 91, pages 1349 to 1358 (1998) by Bosio et al.; Rev. Prat., Vol. 47, pages 2146 to 2152 (1997) by Garot et al.; and Fortschr. Med., Vol. 115, pages 30 to 34 (1997) by Schwinger et al.
In regards to chronic heart failure, perhaps as many as 20 million individuals in the United States have an asymptomatic impairment of cardiac function and are likely to develop symptoms in the next 1 to 5 years. At this stage of heart failure, a reliable index of cardiac contractility is required for an early identification and appropriate treatment to achieve the greatest impact on individual and public health, as, for example, described in Am. J. Cardiol., Vol. 83, pages 1A to 38A (1999) by Parker et al.
In more advanced stages of heart failure, ventricular function parameters are measured to identify the severity of the cardiac abnormality. In this setting, ejection fraction is widely used. However, it has no good correlation with the physical capacity of the patient, as, for example, described in Circulation, Vol. 87 (Suppl. VI), pages VI-88 to VI-93 (1993) by Smith et al.; and Am. J. Cardiol., Vol. 47, pages 33 to 39 (1981) by Franciosa et al. There is debate about the value of repeated measurement of ejection fraction to evaluate the course, prognosis or therapeutic response, as, for example, described in the above-mentioned reference by Parker et al. It is expected that a more refined assessment of cardiac contractility, together with a better knowledge of the peripheral circulation and the neuro-endocrine axes, will improve the evaluation and treatment of these patients.
In severe valve diseases with striking modifications in cardiac loads, adequate information in relation to cardiac contractility, but different to the typically used ejection phase indices, is most important to choose the proper time for surgical treatment, as, for example, described in Heart Disease, Braunwald (ed.), W. B. Saunders Company, Philadelphia, 1977, pages 1007 to 1076, by Braunwald.
Contractility or inotropic state of the heart refers to a fundamental property of cardiac tissue and represents the intensity of the active state of the muscle. The level of the inotropic state is given by the interaction of calcium ions and the contractile protein reflecting the level of activation and the formation and cycling of the cross bridges between actin and myosin filaments, as, for example, described in Heart Disease, Brunwald (ed.), W. B. Saunders Company, Philadelphia, 1977, pages 421 to 444 by Little et al. This interaction is able to be widely modified by multiple and simultaneous factors such as force-frequency relation, circulating catecholamines, sympathetic nerve impulses, anoxia, hypercapnia, acidosis, pharmacologic intervention, etc., as, for example, described in J. Cardiovasc. Pharmacol., Vol. 26 (Suppl. 1), pages S1 to S9 (1995) by Opie. However, no absolute measure of myocardial contractility exists.
Many indices have been proposed as measures of left ventricular contractile function, analyzing the behavior of changes in pressure and/or volume during the isovolumetric or ejection phase of the left ventricular systole. Some of these indices are shown in Table 1.
Most of these indices of cardiac contractility, such as maximum rate of rise of dP/dt, EF, and Vcf, are highly sensitive to acute inotropic changes, as, for example, described in From Cardiac Catheterization Data to Hemodynamic Parameters, F. A. Davis Company, Philadelphia, 1988, by Yang et al.; J. Clin. Invest., Vol. 41, page 80 (1962) by Gleason et al.; Am. J. Cardiol., Vol. 31, page 415 (1973) by Krayenbuehl et al.; Circ. Res., Vol. 56, page 808 (1985) by Little; and Circulation, Vol. 76, page 1422, by Kass et al. However, these indices are markedly modified by preload or afterload alterations, as described, for example, in the above-mentioned references by Gleason et al., Little, and Kass et al. To overcome these limitations, some modifications of these indices have been proposed, such as for dP/dt/P, dP/dt/DP, VPM, stroke volume, MNSER, and FE or Vcf/end-systolic stress, which make them less sensitive, though still sensitive, to changes in loads, as, for example, described in Circulation, Vol. 44, page 47 (1971) by Mason et al.; Cardiovasc. Res., Vol. 8, page 299 (1974) by Davidson et al.; Circulation, Vol. 53, page 293 (1976) by Quinones et al.; Am. J. Physiol., Vol. 240, page H80 (1981) by Carabello et al.; Ann. Intern. Med., Vol. 99, page 750 (1983) by Borow et al.; J. Am. Coll. Cardiol., Vol. 4, page 715 (1984) by Colan et al.; Circulation, Vol. 73, page 47 (1986) by Wisenbaugh et al.; Circulation, Vol. 78, page 68 (1988) by Mirsky et al.; Ann. Intern. Med., Vol. 108, page 524 (1988) by Lang et al.; and J. Am. Coll. Cardiol., Vol. 20, page 787 (1992) by Borow et al. Even Vmax, which was originally proposed as being independent of load index of cardiac contractility, has theoretical and practical limitations, and it is no longer used for clinical purposes, as, for example, described in Ann. Rev. Physiol., Vol. 34, page 47 (1972) by Ross et al.
Another way to assess cardiac contractility is by analyzing the end-systolic pressure/volume relation (ESPVR or ESP/ESV). The generation of variably afterloaded beats allows determination of several relationships. The slope of this line, usually known as Ees or Emax, denotes the maximum stiffness or elastance of the left ventricle, as, for example, described in Circ. Res., Vol. 35, pages 117 to 126 (1974) by Suga et al.; and Circulation, Vol. 69, pages 1058 to 1064 (1984) by Carabello et al. The slope and/or position of the ESPVR respond to changes in myocardial contractile state, as for example, described in Circulation, Vol. 69, pages 1058 to 1064 (1984) by Carabello et al.; and Cardiovasc. Res., Vol. 9, pages 447 to 455 (1975) by Mahler et al. This index is independent of preload, and afterload is the controlled variable, as, for example, described in the above-mentioned reference by Suga et al. However, it is not possible to know the resting value of the relationship since alterations in the afterload are required to obtain the slope of the ESPVR. This slope behaves as a straight line for only part of the range of the physiologic values of afterload, as, for example, described in Am. J. Physiol., Vol. 252, pages H1218 to H1227 (1987) by Burkhoffet al.; and Circulation, Vol. 79, pages 167 to 178 (1989) by Kass et al. Additionally, no normal value of this slope has been established, and this technique is less sensitive than the isovolumetric and ejection phase indices to assess changes in the inotropic state of the heart, as, for example, described in Circulation, Vol. 76, pages 1115 to 1126 (1987) by Crottogini et al.; and Circulation, Vol. 76, pages 1422 to 1436 (1987) by Kass et al.
U.S. Pat. No. 5,400,793 to Wesseling describes a method of determining the stroke volume and cardiac output of the human heart from a pulse-type blood-stream pressure signal. U.S. Pat. No. 5,265,165 to Frank et al. describes a method and apparatus for continuous measurement of cardiac output by analyzing the blood pressure signal. U.S. Pat. Nos. 5,535,753 and 5,647,369, both to Petrucelli et al., describe apparatus and methods for non-invasively measuring cardiovascular system parameters involving sensing a time varying arterial pressure pulse waveform.
U.S. Pat. No. 5,584,298 to Kabal describes a noninvasive method for calculating stroke volume and cardiac output of a human heart using computerized algorithms. U.S. Pat. No. 5,758,652 to Nikolic describes a system and method for measuring the heart condition of a patient by utilizing blood pressure signals. U.S. Pat. No. 5,836,884 to Chio describes a method for determining the cardiovascular condition of a patient by determining peripheral resistance and diastolic flow velocity of the patient.
U.S. Pat. Nos. 5,390,679 and 5,797,395, both to Martin, relate to a cardiac output determining device and method which senses an arterial pressure waveform and compares the sensed waveform to a plurality of stored waveforms representative of known states. U.S. Pat. No. 5,913,826 to Blank describes an apparatus and method for assessing the cardiovascular status of a mammal by utilizing arterial pressure waveforms and systolic and diastolic pressures.
In summary, there are no simple and reliable indices of cardiac contractility, since they are not load independent. The most precise indices (dP/dt, Vmax, or Ees) require invasive and/or sophisticated techniques and usually no normal values have been defined. These indices have been more useful in assessing directional changes in cardiac contractility during acute interventions.
Cardiac contractility is the fundamental parameter of cardiac function, however its adequate assessment is precluded by methodological difficulties. The stroke volume (amount of blood ejected in each beat) is determined by three factors: cardiac contractility, preload, and afterload. Excluding cardiac contractility, the other three parameters may be properly quantified by known techniques. This invention provides methods and measurement systems for assessing the cardiac contractility of a cardiovascular system from the relationship of these other three, usually measurable variables.
One aspect of the present invention pertains to methods of determining the cardiac contractility of a cardiovascular system, which methods comprise the steps of (a) determining the stroke volume of the cardiovascular system; (b) determining the preload of the cardiovascular system; (c) determining the afterload of the cardiovascular system; and (d) utilizing the values of the stroke volume, the preload, and the afterload to calculate the cardiac contractility. In a preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the preload, the value of the afterload, and the value of the cardiac contractility represent a length of one of the edges of each triangle in a tetrahedron, and the value of the stroke volume is represented by the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron. In one embodiment, the value of the preload comprises a parameter selected from the group consisting of end-diastolic volume, end-diastolic volume index, end-diastolic pressure, pulmonary capillary pressure, and end-diastolic stress. In one embodiment, the value of the afterload comprises a parameter selected from the group consisting of arterial pressure, arterial impedance, vascular resistance, and systolic stress.
Another aspect of the present invention pertains to methods of determining the cardiac contractility of a cardiovascular system, which methods comprise the step of utilizing the values representing the stroke volume, the preload, and the afterload of the cardiovascular system to calculate the cardiac contractility. In a preferred embodiment, the calculation utilizes a mathematical relationship where the value of the preload, the value of the afterload, and the value of the cardiac contractility represent a length of one of the edges of each triangle in a tetrahedron, and the value of the stroke volume is represented by the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron.
Another aspect of the present invention pertains to a measurement system for determining the cardiac contractility of a cardiovascular system, comprising (a) a system which determines the stroke volume of the cardiovascular system and which provides a signal representative of the stroke volume; (b) a system which determines the preload of the cardiovascular system and which provides a signal representative of the preload; (c) a system which determines the afterload of the cardiovascular system and which provides a signal representative of the afterload; and (d) a processor which (i) receives the signal representing the stroke volume; (ii) receives the signal representing the preload; (iii) receives the signal representing the afterload; and (iv) calculates the cardiac contractility from the signal representing the stroke volume, the signal representing the preload, and the signal representing the afterload. In a preferred embodiment, the mathematical relationship utilized to calculate the cardiac contractility comprises the preload, the afterload, and the cardiac contractility representing a length of one of the edges of each triangle in a tetrahedron, and the stroke volume representing the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron. In one embodiment, the signal representing the preload comprises a parameter selected from the group consisting of end-diastolic volume, end-diastolic volume index, end-diastolic pressure, pulmonary capillary pressure, and end-diastolic stress. In one embodiment, the signal representing the afterload comprises a parameter selected from the group consisting of arterial pressure, arterial impedance, vascular resistance, and systolic stress.
Still another aspect of this invention pertains to a measurement system for determining the cardiac contractility of a cardiovascular system, comprising a processor which (a) receives an input value representing the stroke volume of the cardiovascular system; (b) receives an input value representing the preload of the cardiovascular system; (c) receives an input value representing the afterload of the cardiovascular system; and (d) utilizes the input values representing the stroke volume, the preload, and the afterload to calculate the cardiac contractility. In a preferred embodiment, the mathematical relationship utilized to calculate the cardiac contractility comprises the input value representing preload, the input value representing afterload, and the cardiac contractility representing a length of one of the edges of each triangle in a tetrahedron, and the input value representing the stroke volume representing the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron.
The performance of the left ventricle as a pump depends on the contraction of the sarcomeres in the myocardium as well as the loading conditions. The factors controlling myocardial function or shortening are myocardial contractility, afterload, and preload, as, for example, described in Am. J. Physiol., Vol. 202, pages 931 to 939 (1962) by Sonnenblick; Prog Cardiovasc. Dis., Vol. 16, pages 337 to 361 (1973) by Brutsacrt et al.; and Mechanics of Contraction of the Normal and Failing Heart, Braunweld (ed.), Little, Brown and Company, Boston, 1976, pages 39 to 71, by Braunwald et al. Preload is proportional to the stretch of the myocardium prior to stimulation and reflects the initial sarcomera length, and afterload is the load that the myocardium must bear to contract, as, for example, described in Mechanics of Contraction of the Normal and Failing Heart, Braunwald (ed.), Little, Brown and Company, Boston, 1976, pages 39 to 71, by Braunwald et al. Cardiac contractility reflects the level of activation and the formation and cycling of the cross bridges between actin and myosin filaments, as, for example, described in Heart Disease, Braunwald (ed.), W. B. Saunders Company, Philadelphia, 1997, pages 421 to 444, by Little et al.
For the heart as a chamber, myocardial shortening is expressed as the amount of blood ejected or stroke volume. In these conditions, preload is properly reflected by the end-diastolic volume, as, for example, described in Circ. Res., Vol. 35, pages 517 to 526 (1974) by Sonnenblick et al.; and Circ. Res., Vol. 21, pages 423 to 431 (1967) by Sonnenblick et al. Afterload can be represented as aortic impedance, as, for example, described in Circ. Res., Vol. 14, pages 283 to 293 (1964) by Wilcken et al.; Circ. Res., Vol. 40, page 451 (1977) by Nichols et al.; and J. Hypertension, Vol. 10, page 53 (1992) by O""Rourke et al. Afterload can also be represented as systemic vascular resistance, as, for example, described in Circ. Res., Vol. 9, pages 1148 to 1155 (1961) by Imperial et al.; and in xe2x80x9cClinical Measurement of Vascular Resistance and Assessment of Vasodilator Drugsxe2x80x9d in Cardiac Catheterization, Angiography and Intervention, Grossman and Baim (ed.), Lea and Febiger, Philadelphia, 1991, page 143, by Grossman. In chronic conditions with alterations in the configuration of the left ventricle, afterload is adequately expressed as systolic stress, as, for example, described in Biophys. J., Vol. 9, pages 189 to 208 (1969) by Mirsky; Am. J. Cardiol., Vol. 34, pages 627 to 634 (1974) by Gould et al.; Circ. Res., Vol. 49, pages 829 to 842 (1981) by Yin; and Am. J. Physiol., Vol. 264, pages H1411 to H1421 (1993) by Regen et al. In the normal heart, the systolic blood pressure can be used as an afterload index since it determines the end-systolic volume, as, for example, described in Circ. Res., Vol. 35, pages 117 to 126 (1974) by Suga et al.; Circ. Res., Vol. 43, pages 677 to 687 (1978) by Sugawa; and Circulation, Vol. 69, pages 1058 to 1064 (1984) by Carabello et al. Only cardiac contractility remains as an elusive variable, with remarkable difficulties in its quantification as previously discussed herein.
Heart rate is the other fundamental variable of cardiac function, but its final effect on the stroke volume is mediated by alterations in loads, as, for example, described in Br. Heart J., Vol. 57, pages 154 to 160 (1987) by Pierard et al. Its final effect on the stroke volume is also mediated by alterations in contractility (force-frequency relation), as, for example, described in Arb. Physiol. Inst. Lpz., Vol. 6, page 139 (1871) by Bowditch; Circulation, Vol. 88, pages 2700 to 2704 (1993) by Mulleri et al.; Circulation, Vol. 88, pages 2962 to 2971 (1973) by Cooper; and Circ. Res., Vol. 75, pages 434 to 442 (1994) by Hasenfuss et al. Heart rate behaves as a partial independent variable, as, for example, described in Circulation, Vol. 32, pages 549 to 558 (1965) by Ross et al.; and Circulation, Vol. 33, pages 933 to 944 (1966) by Benchimol et al. Heart rate has a clear impact on cardiac output (heart rate multiplied by stroke volume) only at very low or high frequency, as, for example, described in Circ. Res., Vol. 8, pages 1254 to 1263 (1960) by Braunwald et al.
In the present invention, it is recognized that stroke volume is determined by cardiac contractility, preload, and afterload. Excluding cardiac contractility, all the other variables are well quantified by standard techniques. In this invention, we disclose a method and a system by which it is possible to quantify cardiac contractility from its relationship with these other, usually known variables. This is attained by the concept of stroke volume as a solid figure, with a tetrahedron shape and a volume equal to the value of this variable. Preload, afterload, and cardiac contractibility may be represented by a variety of lengths or heights of the sides, triangles, or tetrahedral form of the tetrahedron. Choice of these representations may be made by trying various representations on actual cardiac experimental data and assessing the reliability for measuring the cardiac contractibility. For example, in a preferred embodiment, the three edges that comprise each face of the tetrahedron were assigned to preload, afterload, and cardiac contractility. Knowing the amount of the stroke volume (volume of the figure), and the value of the preload and afterload (as the length of the first and second edge, respectively), the method of this invention calculates the length of the third edge (amount of cardiac contractility) that fits with the volume of the figure. Also, for example, in a most preferred embodiment, the calculation of cardiac contractility utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron.
The present invention comprises a simple and reliable method by which it is possible to assess cardiac contractility from its relationship to stroke volume, preload, and afterload. It comprises the concept of stroke volume as a three dimensional figure with a tetrahedron shape. As described above, in a preferred embodiment, the three edges that comprise the faces of the figure are assigned to preload, afterload, and cardiac contractility. Knowing the amount of stroke volume (volume of the figure) and the values of preload and afterload (as the length of the first and second edge, respectively), the method determines the length of the third edge (or amount of cardiac contractility) that fits with the volume of the figure.
For the construction and calibration of the method of the present invention, the normal values are obtained in basal conditions using any of the standard techniques suitable to measure stroke volume, preload (for example, end-diastolic volume), and afterload (for example, aortic impedance, systemic vascular resistance, systolic stress or systolic blood pressure). The amount of stroke volume is equal to the capacity of the tetrahedron. For preload and afterload, the control values are the normal values with a control value of 100 (units) being assigned to cardiac contractility (with a standard deviation given by the standard deviation of the other variables).
Utilizing this method to evaluate the cardiac contractility in a given patient only requires, for example, the actual values of stroke volume, any of the indices of preload such as end-diastolic volume, and any of the indices of afterload, and the method provides the amount of cardiac contractility, as, for example, described in Example 1.
As described above, in a most preferred embodiment, the value of the preload is represented by the length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, the value of the cardiac contractility is represented by the height of the tetrahedron, and the value of the stroke volume is represented by the volume of the tetrahedron. In order to calculate the value of the cardiac contractility from the value of the other three parameters, the analytical geometry for the volume of the tetrahedron may be used to derive the equation. The volume of the tetrahedron is known to be:   V  =            Area      ⁢              xe2x80x83            ⁢      of      ⁢              xe2x80x83            ⁢      Base      ⁢              xe2x80x83            ⁢      Triangle      *      Height      ⁢              xe2x80x83            ⁢      of      ⁢              xe2x80x83            ⁢      Tetrahedron        3  
where V is the volume of the tetrahedron and the symbol, *, as used herein, pertains to multiplication. In the methods of this invention, V represents the stroke volume (SV), and the height of the tetrahedron represents the value of cardiac contractility (C). The area of the base triangle of the tetrahedron is given by,       Area    ⁢          xe2x80x83        ⁢    of    ⁢          xe2x80x83        ⁢    Base    ⁢          xe2x80x83        ⁢    Triangle    =            Length      ⁢              xe2x80x83            ⁢      of      ⁢              xe2x80x83            ⁢      Base      *      Height      ⁢              xe2x80x83            ⁢      of      ⁢              xe2x80x83            ⁢      Base      ⁢              xe2x80x83            ⁢      Triangle        2  
Representing the length of base by preload (PRE) and the height of base triangle by afterload (AFTER), the equation converts to,       Area    ⁢          xe2x80x83        ⁢    of    ⁢          xe2x80x83        ⁢    Base    ⁢          xe2x80x83        ⁢    Triangle    =            PRE      *      AFTER        2  
Substituting SV for V and C for the height of the tetrahedron and inserting the converted equation for the area of the base triangle, the equation becomes,   SV  =            PRE      *      AFTER      *      C        6  
Solving for C, the equation then becomes,   C  =            SV      *      6              PRE      *      AFTER      
Thus, one aspect of the present invention pertains to methods of determining the cardiac contractility of a cardiovascular system, which methods comprise the steps of (a) determining the stroke volume of the cardiovascular system; (b) determining the preload of the cardiovascular system; (c) determining the afterload of the cardiovascular system; and (d) utilizing the values of the stroke volume, the preload, and the afterload to calculate the cardiac contractility. In a preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the preload, the value of the afterload, and the value of the cardiac contractility represent a length of one of the edges of each triangle in a tetrahedron, and the value of the stroke volume is represented by the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron. In one embodiment, the value of the preload comprises a parameter selected from the group consisting of end-diastolic volume, end-diastolic volume index, end-diastolic pressure, pulmonary capillary pressure, and end-diastolic stress. In one embodiment, the value of the afterload comprises a parameter selected from the group consisting of arterial pressure, arterial impedance, vascular resistance, systolic pressure, and systolic stress.
Another aspect of the present invention pertains to methods of determining the cardiac contractility of a cardiovascular system, which methods comprise the step of utilizing the values representing the stroke volume, the preload, and the afterload of the cardiovascular system to calculate the cardiac contractility. In a preferred embodiment, the calculation utilizes a mathematical relationship where the value of the preload, the value of the afterload, and the value of the cardiac contractility represent a length of one of the edges of each triangle in a tetrahedron, and the value of the stroke volume is represented by the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron.
The methods of this invention disclosed herein provide the clinician with reliable and simple methods to assess cardiac contractility in order to increase the accuracy of the cardiac evaluation and improve the therapeutic management of the cardiovascular disorders. These novel methods allow a simple and reliable evaluation of cardiac contractility based in a comprehensive relationship of the fundamental parameters of ventricular function. Quantification of cardiac contractility by these methods is scarcely modified by loads, allowing a proper identification of inotropic abnormalities. These methods determine the amount of cardiac contractility responsible for an abnormal quantity of stroke volume, therefore providing useful information for diagnostic and therapeutic purposes. Additionally, to supply information about the inotropic state of the heart, these methods only need the input of well known hemodynamic variables, that may be obtained by any of the routinely used invasive or non-invasive techniques, as known in the art of cardiovascular measurements.
Considering that cardiovascular diseases are a leading cause of death, there is a strong need for a proper quantification of cardiac contractility. The methods of the present invention can be incorporated with all equipment and systems known in the art to evaluate ventricular function non-invasively such as echocardiography, radionuclide techniques or nuclear magnetic resonance, as well as in invasive techniques in the catheter lab, intensive care units or in surgery theatres, in order to provide a measurement system for determining the cardiac contractility of a cardiovascular system. These known systems for determining the stroke volume, the preload, the afterload, and other cardiovascular performance features may include or be combined with a suitable processor, such as a computer capable of processing digital signals or even manual calculation using the mathematical relationship of the methods of this invention to provide a measurement system to determine cardiac contractility. The measurement system of this invention may further comprise a display device which receives the value of cardiac contractility from the processor and displays that value, such as a display device comprising a monitor that visually displays the cardiac contractility. Also, the display device may be a recorder that records the cardiac contractility. The measurement system of this invention may operate in real time and may provide a continuous determination of the cardiac contractility of the patient or, alternatively, may operate in a time delay from real time operation.
Thus, one aspect of the present invention pertains to a measurement system for determining the cardiac contractility of a cardiovascular system, comprising (a) a system which determines the stroke volume of the cardiovascular system and which provides a signal representative of the stroke volume; (b) a system which determines the preload of the cardiovascular system and which provides a signal representative of the preload; (c) a system which determines the afterload of the cardiovascular system and which provides a signal representative of the afterload; and (d) a processor which (i) receives the signal representing the stroke volume; (ii) receives the signal representing the preload; (iii) receives the signal representing the afterload; and (iv) calculates the cardiac contractility from the signal representing the stroke volume, the signal representing the preload, and he signal representing the afterload. In a preferred embodiment, the mathematical relationship utilized to calculate the cardiac contractility comprises the preload, the afterload, and the cardiac contractility representing a length of one of the edges of each triangle in a tetrahedron, and the stroke volume representing the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron. In one embodiment, the signal representing the preload comprises a parameter selected from the group consisting of end-diastolic volume, end-diastolic volume index, end-diastolic pressure, pulmonary capillary pressure, and end-diastolic stress. In one embodiment, the signal representing the afterload comprises a parameter selected from the group consisting of arterial pressure, arterial impedance, vascular resistance, and systolic stress.
Still another aspect of this invention pertains to a measurement system for determining the cardiac contractility of a cardiovascular system, comprising a processor which (a) receives an input value representing the stroke volume of the cardiovascular system; (b) receives an input value representing the preload of the cardiovascular system; (c) receives an input value representing the afterload of the cardiovascular system; and (d) utilizes the input values representing the stroke volume, the preload, and the afterload to calculate the cardiac contractility. In a preferred embodiment, the mathematical relationship utilized to calculate the cardiac contractility comprises the input value representing preload, the input value representing afterload, and the cardiac contractility representing a length of one of the edges of each triangle in a tetrahedron, and the input value representing the stroke volume representing the volume of the tetrahedron. In a most preferred embodiment, the calculation of step (d) utilizes a mathematical relationship where the value of the stroke volume is represented by the volume of a tetrahedron, the value of the preload is represented by a length of the base of the base triangle of the tetrahedron, the value of the afterload is represented by the height of the base triangle of the tetrahedron, and the value of the cardiac contractility is represented by the height of the tetrahedron.